tbuckley/cabot-search huggingface dataset:
Prognostic Factors in High-Grade Osteosarcoma of theExtremities or Trunk: An Analysis of 1,702 Patients Treatedon Neoadjuvant Cooperative Osteosarcoma Study GroupProtocols
Authors: Stefan S. Bielack, Beate Kempf-Bielack, Günter Delling, G. Ulrich Exner, Silke Flege, Knut Helmke, Rainer Kotz, Mechthild Salzer-Kuntschik, Matthias Werner, Winfried Winkelmann, Andreas Zoubek, Heribert Jürgens, Kurt Winkler
Journal: Journal of Clinical Oncology (2023)

To define prognostic factors for response and long-term outcome for a wide spectrum of osteosarcomas, extending well beyond those of the typical young patient with seemingly localized extremity disease.
Genomics Reveals Complex Population History and Unexpected Diversity of Eurasian Otters (<i>Lutra lutra</i>) in Britain Relative to Genetic Methods
Authors: Sarah J du Plessis, Mark Blaxter, Klaus-Peter Koepfli, Elizabeth A Chadwick, Frank Hailer
Journal: Molecular Biology and Evolution (2023)

Conservation genetic analyses of many endangered species have been based on genotyping of microsatellite loci and sequencing of short fragments of mtDNA. The increase in power and resolution afforded by whole genome approaches may challenge conclusions made on limited numbers of loci and maternally inherited haploid markers. Here, we provide a matched comparison of whole genome sequencing versus microsatellite and control region (CR) genotyping for Eurasian otters (Lutra lutra). Previous work identified four genetically differentiated "stronghold" populations of otter in Britain, derived from regional populations that survived the population crash of the 1950s-1980s. Using whole genome resequencing data from 45 samples from across the British stronghold populations, we confirmed some aspects of population structure derived from previous marker-driven studies. Importantly, we showed that genomic signals of the population crash bottlenecks matched evidence from otter population surveys. Unexpectedly, two strongly divergent mitochondrial lineages were identified that were undetectable using CR fragments, and otters in the east of England were genetically distinct and surprisingly variable. We hypothesize that this previously unsuspected variability may derive from past releases of Eurasian otters from other, non-British source populations in England around the time of the population bottleneck. Our work highlights that even reasonably well-studied species may harbor genetic surprises, if studied using modern high-throughput sequencing methods.
DPP9 Stabilizes NRF2 to Suppress Ferroptosis and Induce Sorafenib Resistance in Clear Cell Renal Cell Carcinoma
Authors: Kun Chang, Yingji Chen, Xuanzhi Zhang, Wei Zhang, Ning Xu, Bohan Zeng, Yue Wang, Tao Feng, Bo Dai, Fujiang Xu, Dingwei Ye, Chenji Wang
Journal: Cancer Research (2023)

Abstract The KEAP1-NRF2 axis is the principal regulator of cellular responses to oxidative and electrophilic stressors. NRF2 hyperactivation is frequently observed in many types of cancer and promotes cancer initiation, progression, metastasis, and resistance to various therapies. Here, we determined that dipeptidyl peptidase 9 (DPP9) is a regulator of the KEAP1-NRF2 pathway in clear cell renal cell carcinoma (ccRCC). DPP9 was markedly overexpressed at the mRNA and protein levels in ccRCC, and high DPP9 expression levels correlated with advanced tumor stage and poor prognosis in patients with ccRCC. Protein affinity purification to identify functional partners of DPP9 revealed that it bound to KEAP1 via a conserved ESGE motif. DPP9 disrupted KEAP1-NRF2 binding by competing with NRF2 for binding to KEAP1 in an enzyme-independent manner. Upregulation of DPP9 led to stabilization of NRF2, driving NRF2-dependent transcription and thereby decreasing cellular reactive oxygen species levels. Moreover, DPP9 overexpression suppressed ferroptosis and induced resistance to sorafenib in ccRCC cells, which was largely dependent on the NRF2 transcriptional target SLC7A11. Collectively, these findings indicate that the accumulation of DPP9 results in hyperactivation of the NRF2 pathway to promote tumorigenesis and intrinsic drug resistance in ccRCC. Significance: DPP9 overcomes oxidative stress and suppresses ferroptosis in ccRCC by binding to KEAP1 and promoting NRF2 stability, which drives tumor development and sorafenib resistance.
Multiple primary melanoma: risk factors ­reviewed
Authors: Remco van Doorn
Journal: British Journal of Dermatology (2023)

Journal Article Accepted manuscript Multiple Primary Melanoma: Risk Factors Reviewed Get access Remco van Doorn Remco van Doorn Leiden University Medical Center, Department of Dermatology, Leiden, the NetherlandsNetherlands Cancer Institute, Department of Dermatology, Amsterdam, the Netherlands Email:rvandoorn@lumc.nl https://orcid.org/0000-0002-7019-6673 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljad343, https://doi.org/10.1093/bjd/ljad343 Published: 15 September 2023 Article history Received: 07 September 2023 Accepted: 13 September 2023 Published: 15 September 2023
Health-Related Quality of Life With Nivolumab Plus Chemotherapy Versus Chemotherapy in Patients With Advanced Gastric/Gastroesophageal Junction Cancer or Esophageal Adenocarcinoma From CheckMate 649
Authors: Markus Moehler, Hong Xiao, Steven I. Blum, Elena Elimova, David Cella, Kohei Shitara, Jaffer A. Ajani, Yelena Y. Janjigian, Marcelo Garrido, Lin Shen, Kensei Yamaguchi, Tianshu Liu, Michael Schenker, Ruben Kowalyszyn, Arinilda Campos Bragagnoli, Ricardo Bruges, Vincenzo Montesarchio, Roberto Pazo-Cid, Shannon Hunter, Eric Davenport, Jinyi Wang, Kaoru Kondo, Mingshun Li, Lucjan Wyrwicz
Journal: Journal of Clinical Oncology (2023)

In CheckMate 649, first-line nivolumab plus chemotherapy prolonged overall survival versus chemotherapy in patients with advanced/metastatic non-human epidermal growth factor receptor 2 (HER2)-positive gastric/gastroesophageal junction cancer (GC/GEJC) or esophageal adenocarcinoma (EAC). We present exploratory patient-reported outcomes (PROs).
One‐Pot Synthesis of Tumor‐Microenvironment Responsive Degradable Nanoflower‐Medicine for Multimodal Cancer Therapy with Reinvigorating Antitumor Immunity
Authors: Jiamin Sun, Kai Jiang, Yifan Wang, Yuqing Liu, Ting Wang, Shiyue Ding, Xianzhi Zhang, Weiwei Xiong, Fenfen Zheng, Haitang Yang, Jun‐Jie Zhu
Journal: Advanced Healthcare Materials (2023)

Abstract Multimodal cancer therapies show great promise in synergistically enhancing anticancer efficacy through different mechanisms. However, most current multimodal therapies either rely on complex assemblies of multiple functional nanomaterials and drug molecules or involve the use of nanomedicines with poor in vivo degradability/metabolizability, thus restricting their clinical translatability. Herein, a nanoflower‐medicine using iron ions, thioguanine (TG), and tetracarboxylic porphyrin (TCPP) are synthesized as building blocks through a one‐step hydrothermal method for combined chemo/chemodynamic/photodynamic cancer therapy. The resulting nanoflowers, consisting of low‐density Fe 2 O 3 core and iron complex (Fe‐TG and Fe‐TCPP compounds) shell, exhibit high accumulation at the tumor site, desirable degradability in the tumor microenvironment (TME), robust suppression of tumor growth and metastasis, as well as effective reinvigoration of host antitumor immunity. Triggered by the low pH in tumor microenvironment, the nanoflowers gradually degrade after internalization, contributing to the effective drug release and initiation of high‐efficiency catalytic reactions precisely in tumor sites. Moreover, iron ions can be eliminated from the body through renal clearance after fulfilling their mission. Strikingly, it is also found that the multimodal synergistic therapy effectively elicits the host antitumor immunity without inducing additional toxicity. This easy‐manufactured and degradable multimodal therapeutic nanomedicine is promising for clinical precision oncology.
Sustained Release of Nitric Oxide‐Mediated Angiogenesis and Nerve Repair by Mussel‐Inspired Adaptable Microreservoirs for Brain Traumatic Injury Therapy
Authors: Hsiu‐Ching Liu, Chu‐Han Huang, Min‐Ren Chiang, Ru‐Siou Hsu, Tsu‐Chin Chou, Tsai‐Te Lu, I‐Chi Lee, Lun‐De Liao, Shih‐Hwa Chiou, Zhong‐Hong Lin, Shang‐Hsiu Hu
Journal: Advanced Healthcare Materials (2023)

Traumatic brain injury (TBI) triggers inflammatory response and glial scarring, thus substantially hindering brain tissue repair. This process is exacerbated by the accumulation of activated immunocytes at the injury site, which contributes to scar formation and impedes tissue repair. In this study, a mussel-inspired nitric oxide-release microreservoir (MINOR) that combines the features of reactive oxygen species (ROS) scavengers and sustained NO release to promote angiogenesis and neurogenesis is developed for TBI therapy. The injectable MINOR fabricated using a microfluidic device exhibits excellent monodispersity and gel-like self-healing properties, thus allowing the maintenance of its structural integrity and functionality upon injection. Furthermore, polydopamine in the MINOR enhances cell adhesion, significantly reduces ROS levels, and suppresses inflammation. Moreover, a nitric oxide (NO) donor embedded into the MINOR enables the sustained release of NO, thus facilitating angiogenesis and mitigating inflammatory responses. By harnessing these synergistic effects, the biocompatible MINOR demonstrates remarkable efficacy in enhancing recovery in mice. These findings benefit future therapeutic interventions for patients with TBI.
A commentary on ‘Indications for surgical resection of complicated infantile hemangiomas in the β-blocker’s era: a single-institution experience from a retrospective cohort study’
Authors: Tingting Chen, Binbin Ye, Yangxia Xu, Fuzhen Pang
Journal: International Journal of Surgery (2023)

aDepartment of Pediatrics, Tiantai People's Hospital of Zhejiang Province, Zhejiang, China, 317200 bDepartment of Pediatric Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Zhejiang, China, 317000 Data are publicly available. Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Published online ■ ■ *Corresponding author. Address: CHINA. E-mail address: [email protected] (F Pang). This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/
A commentary on ‘Effects of machine perfusion strategies on different donor types in liver transplantation: a systematic review and meta-analysis’
Authors: Gang Tang, Linyu Zhang, Rongxing Zhou
Journal: International Journal of Surgery (2023)

aDivision of Biliary Tract Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China bCenter for Translational Medicine, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Published online ■ ■ *Corresponding author. Address: No. 37 Guo Xue Xiang, Chengdu, Sichuan, 610041, P.R. China. E-mail address: [email protected]; [email protected] (R. Zhou). This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0/
Application and challenges of ChatGPT in interventional surgery
Authors: Zhaorong Wu, Linke Bian, Haigang Geng, Zhigang zheng, Hongye Wang, Bo Zhai
Journal: International Journal of Surgery (2023)

Wu, Zhaorong; Bian, Linke; Geng, Haigang; zheng, Zhigang; Wang, Hongye; Zhai, Bo Author Information
Cardiac Insulin Resistance in Subjects With Metabolic Syndrome Traits and Early Subclinical Atherosclerosis
Authors: Ana Devesa, Valentin Fuster, Ravi Vazirani, Inés García-Lunar, Belén Oliva, Samuel España, Andrea Moreno-Arciniegas, Javier Sanz, Cristina Perez-Herreras, Héctor Bueno, Enrique Lara-Pezzi, Ana García-Alvarez, Vicente Martínez de Vega, Leticia Fernández-Friera, Maria G. Trivieri, Antonio Fernández-Ortiz, Xavier Rossello, Javier Sanchez-Gonzalez, Borja Ibanez
Journal: Diabetes Care (2023)

OBJECTIVE Experimental evidence suggests that metabolic syndrome (MetS) is associated with changes in cardiac metabolism. Whether this association occurs in humans is unknown. RESEARCH DESIGN AND METHODS 821 asymptomatic individuals from the Progression of Early Subclinical Atherosclerosis (PESA) study (50.6 [46.9–53.6] years, 83.7% male) underwent two whole-body 18F-fluorodeoxyglucose positron emission tomography-magnetic resonance (18F-FDG PET-MR) 4.8 ± 0.6 years apart. Presence of myocardial 18F-FDG uptake was evaluated qualitatively and quantitatively. No myocardial uptake was grade 0, while positive uptake was classified in grades 1–3 according to target-to-background ratio tertiles. RESULTS One hundred fifty-six participants (19.0%) showed no myocardial 18F-FDG uptake, and this was significantly associated with higher prevalence of MetS (29.0% vs. 13.9%, P &amp;lt; 0.001), hypertension (29.0% vs. 18.0%, P = 0.002), and diabetes (11.0% vs. 3.2%, P &amp;lt; 0.001), and with higher insulin resistance index (HOMA-IR, 1.64% vs. 1.23%, P &amp;lt; 0.001). Absence of myocardial uptake was associated with higher prevalence of early atherosclerosis (i.e., arterial 18F-FDG uptake, P = 0.004). On follow-up, the associations between myocardial 18F-FDG uptake and risk factors were replicated, and MetS was more frequent in the group without myocardial uptake. The increase in HOMA-IR was associated with a progressive decrease in myocardial uptake (P &amp;lt; 0.001). In 82% of subjects, the categorization according to presence/absence of myocardial 18F-FDG uptake did not change between baseline and follow-up. MetS regression on follow-up was associated with a significant (P &amp;lt; 0.001) increase in myocardial uptake. CONCLUSIONS Apparently healthy individuals without cardiac 18F-FDG uptake have higher HOMA-IR and higher prevalence of MetS traits, cardiovascular risk factors, and early atherosclerosis. An improvement in cardiometabolic profile is associated with the recovery of myocardial 18F-FDG uptake at follow-up.
World Health Organization's low‐intensity psychosocial interventions: a systematic review and meta‐analysis of the effects of Problem Management Plus and<scp>Step‐by‐Step</scp>
Authors: Sarah K. Schäfer, Lea M. Thomas, Saskia Lindner, Klaus Lieb
Journal: World Psychiatry (2023)

Many societies have been recently exposed to humanitarian and health emergencies, which have resulted in a large number of people experiencing significant distress and being at risk to develop mental disorders such as depression, anxiety and post‐traumatic stress disorder. The World Health Organization has released a series of scalable psychosocial interventions for people impaired by distress in communities exposed to adversities. Prominent among these is a low‐intensity transdiagnostic psychosocial intervention, Problem Management Plus (PM+), and its digital adaptation Step‐by‐Step (SbS). This systematic review is the first to summarize the available evidence on the effects of PM+ and SbS. Up to March 8, 2023, five databases were searched for randomized controlled trials examining the effects of PM+ or SbS on distress indicators (i.e., general distress; anxiety, depressive or post‐traumatic stress disorder symptoms; functional impairment, self‐identified problems) and positive mental health outcomes (i.e., well‐being, quality of life, social support/relationships). We performed random‐effects multilevel meta‐analyses on standardized mean differences (SMDs) at post‐intervention and short‐term follow‐up assessments. Our search yielded 23 eligible studies, including 5,298 participants. We found a small to medium favorable effect on distress indicators (SMD=–0.45, 95% CI: –0.56 to –0.34) and a small beneficial effect on positive mental health outcomes (SMD=0.31, 95% CI: 0.14‐0.47), which both remained significant at follow‐up assessment and were robust in sensitivity analyses. However, our analyses pointed to substantial between‐study heterogeneity, which was only partially explained by moderators, and the certainty of evidence was very low across all outcomes. These results provide evidence for the effectiveness of PM+ and SbS in reducing distress indicators and promoting positive mental health in populations exposed to adversities, but a larger high‐quality evidence base is needed, as well as research on participant‐level moderators of the effects of these interventions, their suitability for stepped‐care programs, and their cost‐effectiveness.
20‐year trajectories of positive and negative symptoms after the first psychotic episode in patients with schizophrenia spectrum disorder: results from the <scp>OPUS</scp> study
Authors: Marie Starzer, Helene Gjervig Hansen, Carsten Hjorthøj, Nikolai Albert, Merete Nordentoft, Trine Madsen
Journal: World Psychiatry (2023)

This study aimed to identify the 20‐year trajectories of positive and negative symptoms after the first psychotic episode in a sample of patients with an ICD‐10 diagnosis of schizophrenia spectrum disorder, and to investigate the baseline characteristics and long‐term outcomes associated with these trajectories. A total of 373 participants in the OPUS trial were included in the study. Symptoms were assessed at baseline and after 1, 2, 5, 10 and 20 years using the Scales for the Assessment of Positive and Negative Symptoms. We used latent class growth mixture modelling to identify trajectories, and multinominal regression analyses to investigate predictors of membership to identified trajectories. Five trajectories of positive symptoms were identified: early continuous remission (50.9% of the sample), stable improvement (18.0%), intermittent symptoms (10.2%), relapse with moderate symptoms (11.9%), and continuous severe symptoms (9.1%). Substance use disorder (odds ratio, OR: 2.83, 95% CI: 1.09‐7.38, p=0.033), longer duration of untreated psychosis (OR: 1.02, 95% CI: 1.00‐1.03, p=0.007) and higher level of negative symptoms (OR: 1.60, 95% CI: 1.07‐2.39, p=0.021) were predictors of the relapse with moderate symptoms trajectory, while only longer duration of untreated psychosis (OR: 1.01, 95% CI: 1.00‐1.02, p=0.030) predicted membership to the continuous severe symptoms trajectory. Two trajectories of negative symptoms were identified: symptom remission (51.0%) and continuous symptoms (49.0%). Predictors of the continuous symptoms trajectory were male sex (OR: 3.03, 95% CI: 1.48‐6.02, p=0.002) and longer duration of untreated psychosis (OR: 1.01, 95% CI: 1.00‐1.02, p=0.034). Trajectories displaying continuous positive and negative symptoms were linked to lower neurocognition, as measured by the Brief Assessment of Cognition in Schizophrenia (BACS) (z‐score: –0.78, CI: –1.39 to –0.17, for continuous positive symptoms; z‐score: –0.33, CI: –0.53 to –0.13, for continuous negative symptoms). The same trajectories were also linked to higher use of antipsychotic medication at 20‐year follow‐up (continuous positive symptoms: 78%; continuous negative symptoms: 67%). These findings suggest that the majority of patients with first‐episode schizophrenia spectrum disorder have a trajectory with early stable remission of positive symptoms. Long duration of untreated psychosis and comorbid substance abuse are modifiable predictors of poor trajectories for positive symptoms in these patients. In about half of patients, negative symptoms do not improve over time. These symptoms, in addition to being associated with poor social and neurocognitive functioning, may prevent patients from seeking help.
Comorbidity between major depressive disorder and physical diseases: a comprehensive review of epidemiology, mechanisms and management
Authors: Michael Berk, Ole Köhler‐Forsberg, Megan Turner, Brenda W.J.H. Penninx, Anna Wrobel, Joseph Firth, Amy Loughman, Nicola J. Reavley, John J. McGrath, Natalie C. Momen, Oleguer Plana‐Ripoll, Adrienne O'Neil, Dan Siskind, Lana J. Williams, Andre F. Carvalho, Lianne Schmaal, Adam J. Walker, Olivia Dean, Ken Walder, Lesley Berk, Seetal Dodd, Alison R. Yung, Wolfgang Marx
Journal: World Psychiatry (2023)

Populations with common physical diseases – such as cardiovascular diseases, cancer and neurodegenerative disorders – experience substantially higher rates of major depressive disorder (MDD) than the general population. On the other hand, people living with MDD have a greater risk for many physical diseases. This high level of comorbidity is associated with worse outcomes, reduced adherence to treatment, increased mortality, and greater health care utilization and costs. Comorbidity can also result in a range of clinical challenges, such as a more complicated therapeutic alliance, issues pertaining to adaptive health behaviors, drug‐drug interactions and adverse events induced by medications used for physical and mental disorders. Potential explanations for the high prevalence of the above comorbidity involve shared genetic and biological pathways. These latter include inflammation, the gut microbiome, mitochondrial function and energy metabolism, hypothalamic‐pituitary‐adrenal axis dysregulation, and brain structure and function. Furthermore, MDD and physical diseases have in common several antecedents related to social factors (e.g., socioeconomic status), lifestyle variables (e.g., physical activity, diet, sleep), and stressful live events (e.g., childhood trauma). Pharmacotherapies and psychotherapies are effective treatments for comorbid MDD, and the introduction of lifestyle interventions as well as collaborative care models and digital technologies provide promising strategies for improving management. This paper aims to provide a detailed overview of the epidemiology of the comorbidity of MDD and specific physical diseases, including prevalence and bidirectional risk; of shared biological pathways potentially implicated in the pathogenesis of MDD and common physical diseases; of socio‐environmental factors that serve as both shared risk and protective factors; and of management of MDD and physical diseases, including prevention and treatment. We conclude with future directions and emerging research related to optimal care of people with comorbid MDD and physical diseases.